Young men who have sex with men (YMSM) ages 16-29 are disproportionately affected by HIV, with high prevalence and incidence. While all other risk groups have declining rates of infection, dramatic increases are occurring among YMSM. YMSM are understudied, but preliminary research demonstrates that the HIV epidemic in YMSM forms a syndemic with drug use, violence, and mental health problems. The proposed study will build a dynamic dyadic-network cohort of 1,358 YMSM by hybridizing 2 existing cohorts of YMSM: Project Q2 (aged 20-24) and ChiGuys (aged 16-17). We will expand this unified cohort through the enrollment of serious sexual partners of core participants, thereby creating a dynamic dyadic network. The overarching goal of this proposal is to apply a next generation multilevel model (Network-Individual-Resources model) to understand the syndemic among a cohort of YMSM and inform high-impact HIV prevention with this vulnerable population. To achieve this goal, we propose four specific aims. Aim 1 is to understand how syndemics of substance use, HIV, STIs, mental disorders, and violence develop among YMSM using an accelerated longitudinal design. We will assess youth every 6 months during the transition from late adolescence to early adulthood, to describe the trajectories of syndemic development (including substance use) and use innovative statistical modeling to characterize different trajectories of syndemic development to predict youth most at risk of HIV acquisition. Aim 2 is to determine how dyadic processes influence HIV risk behaviors and transmission among YMSM by enrolling their serious sexual partners into the cohort. We will utilize dyadic data to identify which sexual partner and relationship factors are longitudinally related to unprotected sex and HIV/STI transmission across development. Phylogenetic analyses will link HIV transmissions within dyads to determine what behavioral, partner and dyadic factors predict such transmission. Aim 3 is to describe network and structural influences on syndemic development among YMSM. We will examine how sexual and drug use network structure Men who have sex with men (MSM) are the largest HIV transmission group in the U.S. and infections are increasing most among young MSM (YMSM). The objective of this proposal is to build a large and innovative dynamic dyadic-network cohort of YMSM and their serious sexual partners in order to delineate multilevel influences on HIV and substance use. This cohort will serve as a strong resource platform for a wide range of future innovative research efforts and will inform behavioral and biomedical HIV prevention interventions for YMSM.